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Two-step role for mutant TERT promoters Telomeres preserve genomic stability by preventing chromosomal fusions. The recent discovery that human tumors harbor mutations in the promoter region of the telomerase gene ( TERT ) produced a flurry of research aimed at elucidating the role of these mutations in cancer development. Chiba et al. present data that reconcile many of the conflicting results reported to date (see the Perspective by Shay). In human melanoma samples and a fibroblast model, TERT promoter mutations acted in two steps. First, the mutations allowed cells to proliferate with short telomeres. This fueled genomic instability and up-regulation of telomerase expression, leading to uncontrolled cell proliferation. Science , this issue p. 1416 ; see also p. 1358

Pol II Micro Clusters In higher eukaryotes, messenger RNA (mRNA) synthesis is thought to involve foci of clustered RNA polymerase II (Pol II) called transcription factories. However, clustered Pol II have not been resolved in living cells, raising the debate about their existence in vivo and what role, if any, they play in nuclear organization and regulation of gene expression. Cisse et al. (p. 664 , published online 4 July; see the Perspective by Rickman and Bickmore ) developed single-molecule in vivo analyses revealing the distribution and dynamics of Pol II clustering in living cells. Pol II clusters were smaller than the diffraction limit (

Understanding gene expression requires the ability to follow the fate of individual molecules. Here we use a cellular system for monitoring messenger RNA (mRNA)expression to characterize the movement in real time of single mRNA-protein complexes (mRNPs) in the nucleus of living mammalian cells. This mobility was not directed but was governed by simple diffusion. Some mRNPs were partially corralled throughout the nonhomogenous nuclear environment, but no accumulation at subnuclear domains was observed. Following energy deprivation, energy-independent motion of mRNPs was observed in a highly ATP-dependent nuclear environment; movements were constrained to chromatin-poor domains and excluded by newly formed chromatin barriers. This observation resolves a controversy, showing that the energetic requirements of nuclear mRNP trafficking are consistent with a diffusional model.